Back and forth on beta-blockers

Hospitalists have new evidence to balance the risks and benefits of beta-blockers in
certain patients. In a recent study of nearly 16,000 older nursing home residents,
starting beta-blockers after an acute myocardial infarction (AMI) lowered the 90-day
risk of mortality by about 25%, but significantly increased the likelihood of functional
decline, especially when patients had moderate or severe cognitive impairment or severe
functional dependency.

“We think this is a new discovery,” said Michael A. Steinman, MD, FACP,
professor of medicine in the division of geriatrics at the University of California,
San Francisco, who reported the findings in the February 2017 JAMA Internal Medicine.

Evidence and the experts are more certain about the value of beta-blockers for most
patients with heart failure. Image by Thinkstock

Beta-blockers can cause fatigue, dizziness, and a decreased sense of well-being, which
might be “the straw that broke the camel's back” for frail, elderly
patients, Dr. Steinman said. “This might be an example of how adverse effects
that are tolerable in a relatively robust older adult can tip a vulnerable older adult
‘over the edge’ into bad outcomes.”

That means that among the many factors determining whether a patient should take beta-blockers,
hospitalists should also now consider older patients' functional and cognitive status.

For AMI patients with no more than mild dementia and at least moderate functional
abilities, beta-blockade seems to prevent mortality without leading to functional
decline, Dr. Steinman said. But if patients do not meet those criteria, “decisions
about beta-blocker use should be driven by goals of care. If patients strongly value
staying alive, beta-blockers are a good choice. But if the patient values preserving
function more than prolonging lifespan, it may be reasonable not to prescribe a beta-blocker.”

Questions on post-AMI use

Such findings challenge decades-old notions about the universal benefits of beta-blockers
after AMI, said Jeffrey Goldberger, MD, FACP, chief of the cardiovascular division
at the University of Miami in Florida. “In patients with recent MI, the major
new questions are: Do all patients require treatment? What is the optimal dose? How
long do patients need to be treated?” he said.

When considering whether to prescribe a beta-blocker in a patient hospitalized with
cardiovascular disease, including AMI, Dr. Goldberger recommends asking, “Will
it make the patient feel better? Will it improve survival? Will it prevent other cardiovascular
morbidity, such as hospitalization for heart failure?”

Most patients with AMI should start a beta-blocker in the hospital, but optimal dosing
remains a question, he noted. In a study of nearly 7,000 patients with acute AMI,
low-dose beta-blockers improved two-year survival as effectively as the higher doses
typically used in clinical trials, Dr. Goldberger reported in the September 29, 2015, Journal of the American College of Cardiology. The findings highlight the need for more research on appropriate beta-blocker dosing
after AMI, he concluded.

How long to continue beta-blockers after AMI also remains uncertain. There is no clear
evidence supporting beta-blockade beyond one year in patients with a history of AMI
without left ventricular dysfunction, angina, or dysrhythmia, experts noted in an
editorial accompanying Dr. Steinman's study. Clinicians also lack protocols on tapering
therapy and solid data on the potential benefits and harms of doing so, the editorialists
noted.

Accordingly, they suggested a five-step approach to deciding whether to taper medications
such as beta-blockers. Clinicians and patients can list all prescriptions and the
reason for each, evaluate the overall risks of drug-induced harm, consider whether
each drug can be discontinued, and decide which, if any, to stop. Finally, they can
begin a discontinuation regimen with careful follow-up, the editorialists advised.

Heart failure

The evidence and the experts are more certain about the value of beta-blockers for
most patients with heart failure. In a study of more than 2,000 Medicare beneficiaries
hospitalized with heart failure and ejection fraction below 45%, beta-blockers at
discharge were associated with a 70% decrease in the risk of mortality at 30 days
and a 20% decrease at four years, investigators reported in the July 2015 American Journal of Medicine.

“The evidence for long-term use of beta-blockade in patients with reduced ejection
fraction, along with [angiotensin-converting enzyme] inhibitors and aldosterone antagonists,
is some of the most compelling that we have in internal medicine in terms of absolute
risk reduction for mortality,” said Frank Merritt, MD, a hospitalist and instructor
of medicine at the University of Colorado Anschutz Medical Center in Aurora. For these
patients, hospitalists play a crucial role by starting beta-blockers before discharge,
he said. The American Heart Association recommends this “common-sense approach,”
which helps ensure this step is not missed during follow-up visits, he added.

Dr. Merritt usually prescribes these patients beta-blockers for at least one month.
But beta-blockers are not always appropriate in heart failure, he noted. Because beta-blockers
reduce short-term cardiac output, hospitalists should be “extremely cautious”
about starting or resuming them in patients with severely decompensated heart failure,
especially those who recently received inotropes and have not yet been adequately
diuresed. These cases merit input from a cardiologist, Dr. Merritt emphasized.

The field also lacks robust evidence on whether to continue or temporarily stop beta-blockers
during acute worsening of heart failure, he said. For patients with hypotension without
organ hypoperfusion, the beta-blocker dose might be reduced. But in the “extreme
example of cardiogenic shock, it seems logical that beta-blockers should be temporarily
discontinued, although some cardiologists may just reduce the dose of beta-blocker
and add a non-beta-agonist inotrope, such as milrinone.”

Another question is how to manage beta-blockers in patients with chronic heart failure
and reduced ejection fraction who are hospitalized for other reasons, such as sepsis
or severe blood loss. “Generally, if a patient is hemodynamically unstable
or if you are concerned for impending decompensation, it makes sense to temporarily
hold beta-blockade,” Dr. Merritt said. “Again, there is no randomized
evidence to guide us.”

Coronary artery disease

For patients with coronary artery disease who have neither heart failure nor a history
of MI, recent research suggests that beta-blockers don't prevent cardiovascular events.
There are post-hoc analyses of trials, observational studies, and recent meta-analyses
to support this conclusion, according to William Boden, MD, scientific director of
the Clinical Trials Network, MAVERIC, at the VA New England Healthcare System and
professor of medicine at the Boston University School of Medicine. “There is
mounting evidence that we need to be more selective and judicious in prescribing beta-blockers
to patients hospitalized for cardiovascular disease,” he added.

He cited a study of over 750,000 patients, published in the August 22, 2016, JACC: Cardiovascular Interventions in which beta-blockers failed to improve cardiovascular outcomes 30 days and three
years after elective percutaneous coronary intervention. Findings like these raise
questions about extrapolating the “putative benefits of beta-blockers to all
patients with stable coronary artery disease,” Dr. Boden said. Still, this
population is increasingly receiving beta-blockers, he noted. “For years, clinicians
have extrapolated the evidence of beta-blocker benefit from older post-MI trials and
applied it to all patients with coronary artery disease,” he wrote in an editorial
that accompanied the study.

This overprescribing results mainly from guidelines that broadly recommend beta-blockers
in coronary artery disease, despite a lack of rigorous data showing that they benefit
the large subsets of patients without AMI, reduced left ventricular systolic function,
or ongoing angina, according to Dr. Boden. He finds it very hard to accept such recommendations,
he said. “If we are supposed to practice evidence-based medicine, the evidence
is either weak or lacking that the majority of patients with coronary artery disease
derive any meaningful clinical benefit from beta-blockers.”

Dr. Boden does recommend considering beta-blockers in coronary artery disease with
serious or complex polymorphic or sustained ventricular arrhythmia, he said. “Most
of these patients would also be candidates for an implantable cardioverter/defibrillator
to prevent sudden cardiac death, but even with an ICD implanted in such patients,
I would favor continuing a beta-blocker indefinitely.”

Who does what?

Shifting evidence about the risks and benefits of beta-blockers highlights the need
for hospitalists to seek input from multiple sources when deciding how to treat complex
cases, the experts said.

“Collaborative decision making among physicians is generally the best approach,”
Dr. Steinman stressed. “By the same token, we should not simply be punting
decisions to someone else—that often results in nobody having ownership of
the patient.”

Accordingly, cardiologists should help guide decisions for patients with advanced
heart failure who probably cannot tolerate beta-blockade or who have contraindications
such as borderline hypotension or heart block, said Dr. Merritt. But hospitalists
should take the lead in prescribing beta-blockers for straightforward indications,
such as heart failure in the setting of reduced ejection fraction, he said.

Hospitalists should also talk with primary care clinicians about the reasons for beta-blockade
and the importance of titrating medication if needed, he added. Primary care clinicians
also can help hospitalists understand potential treatment barriers, such as past issues
with cost, health knowledge, or adherence, he said.

Dr. Steinman agreed, noting that physicians make mistakes when they don't consider
or have access to their patients' full story. “The primary care clinician can
provide valuable insights into a patient's goals of care, abilities at home, and so
forth,” he said. “The hospitalist can use this information to help make
a high-quality, patient-centered treatment decision in the acute setting.”

ACP Hospitalist provides news and information for hospitalists, covering the major issues in the field. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated.